What do the terms "drug-specific response/remission rate" and "placebo" really mean?

This column addresses two important clinical trial issues in psychiatry. Placebo is frequently misrepresented by the media as representing nothing. In fact, placebo represents everything except the investigational treatment. That is an important distinction. The second is the concept of the drug-specific response/remission rate. While manufacturers frequently cite the overall response/remission rate observed in the group treated with their drug in their clinical trials, that is not the true rate specifically attributable to the drug. Instead, it represents the combined rate due to both the drug and the non-drug (or "placebo") therapeutic aspects of the trial. To determine the drug-specific response/remission rate, the placebo response/remission rate must be subtracted from the overall response/remission rate observed in the drug treated group. That is because the drug treated group receives both the therapeutic benefit of the drug and all of the nondrug therapeutic benefit of the trial (i.e., the "placebo" condition). Viewed from this perspective, only about one out of four patients with major depression responds specifically to either selective serotonin or serotonin-norepinephrine reuptake inhibitors. These principles are important if one is to put the recent controversy about the effectiveness of modern antidepressant treatment into perspective. The critical issue is not how good the drugs are but rather how serious our diseases are. When evaluating the current antidepressants, the principal issue is not how many patients with major depression they treat but instead how well they treat the patients they do treat. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study has clearly documented that approximately 40% of patients with major depression do not respond to existing antidepressants. That finding is consistent with the concept that there are likely many forms of depressive illness, only a fraction of which are responsive to drugs that work via effects on biogenic amines.